The quantification of chemical and biochemical components in aqueous fluids, and particularly in biological fluids such as whole blood or urine and in biological fluid derivatives such as serum and plasma, is of ever increasing importance. Important applications exist in medical diagnosis and treatment and in the quantification of exposure to therapeutic drugs, intoxicants, hazardous chemicals and the like. These applications include the detection and quantification of an increasing variety of certain circulating antibodies, cancer-related metabolites, genetically derived chemical tracers, and hormones emitted during events such as pregnancy. In many instances, the amounts of materials being determined are minuscule in the range of a microgram or less per deciliter.
One common medical test is the measurement of blood glucose levels by diabetics which is more fully described in U.S. Pat. No. 5,859,937 ('937) of H. Nomura and herein incorporated by reference. Portions of the teachings of the '937 patent are used herein for the sake of completeness. The glucose determination, as described in the '937 patent, typically entails the diabetic piercing the skin of his or her finger with a lance, followed by squeezing or expression of a blood droplet. The blood droplet is then transferred to a reagent pad or test strip. The amount of blood that is conveniently expressed from a finger prick is governed by the size and depth of penetration of the lance. Too small a nick results in an inadequately sized blood sample for the intended analysis. Conversely, too deep a nick results in an oversized blood sample. Pain is experienced in the lancing procedure, and the degree of pain is associated with the size and depth of penetration of the lance.
The teachings of the '937 patent provides a textured site allowing for an increased surface area, compared to other prior art devices, for use in blood sampling. The increased surface area provides an advantage relating to minimizing the invasive feature of glucose testing because the surface area being very small, greatly reduces the level of analyte-responsive needed to be deposited to perform the glucose determination. Increased surface area allows one to utilize a small blood droplet, for instance, a droplet having a volume of one (1) to five (5) microliters, or preferably 1 to 2.5 microliters. The '937 patent allows for a reduction relative to the prior art thereof, of about one-fifth to about one-tenth of the fluid volume necessary blood glucose sensing. It is desired that further improvements to the surface area be provided, so as to correspondingly reduce the amount of blood necessary for determination of glucose for diabetics.
The '937 patent provides a textured surface using various means, such as ion beam sputtering, plasma etching including atomic oxygen plasma, physical abrasion, chemical etching, sputtering or ablation by high energy beams, or deposition of dendritic-like structures thereon. The textured surface of the '937 patent is intended to provide a means for separating cellular components in blood from the plasma of the blood so as to allow optical sensing of the glucose concentration in the blood. The processes described in the '937 patent for developing the textured surface need to produce a cone or pillar structure at the ends of optical fibers or other sensing surfaces which are sufficiently close—so as to prevent the cellular components from entering the microscopic valleys between the cones or pillars so that optical sensing of the glucose concentration can be performed. Also, it is desired to have a sufficiently high aspect ratio (height to width) of cones or pillars to allow sufficient surface area for optical determination of the glucose concentration in the blood.
In pursuit for finding desired pillar structures for the textured surfaces, some of the different processes mentioned in the '937 patent were investigated and may be further described with reference to FIG. 1 herein, which illustrates a Scanning Electron Microscope image of the end of a polymethylmethacrylate optical fiber that was textured by the use of thermal energy (<0.5 eV) atomic oxygen through salt dust for enhancing texturing.
The disadvantages of prior art results shown in FIG. 1 is that the craters produced were too wide to prevent cellular blood components from entering the optical sensing areas and the aspect ratio (height to width) of the surface features does not offer high gains in surface area relative to flat surfaces. As can be seen in FIG. 1, the cone or crater ridges are approximately 20-30 microns apart far too much to achieve their desired goals. More particularly, the spacing between cones or ridges needs to be ≦5 microns to block the entry of blood cells into the cone valleys. Thus, the craters did not provide separation of the plasma from the blood in the areas of the valleys between the cones or pillars where optical sensing of the glucose concentration needs to occur. Use of thermal energy (<0.5 eV) atomic oxygen, sometimes referred to as isotropic thermal energy, to texture the surfaces of clear polymers such as polymethylmethacrylate, polystyrene or other hydrocarbon polymer (even with the use of small particle salt shielding) causes wide almost hemispherical craters to form surface features which are only as high as they are wide. The aspect ratio of only approximately one (1) requires greater volume blood samples than desirable. It is desired that textured surfaces for optical sensors used for blood testing be provided that provide cones or pillars that are spaced apart from each other by less than 5 microns, preferably about 1 micron, and having an aspect ratio (height to width) of greater than one (1).
Another process related to optical fibers is disclosed in U.S. Pat. No. 6,200,737B1 ('737B1) of Walt et al that employs photolithograph. The cost of using photolithography on the ends of multiple bundle fibers is exceedingly high for blood glucose monitoring because it is extremely difficult to simply stack a half million of the multiple bundle fibers together to be used for blood glucose monitoring and perform photolithography thereon as disclosed in the '737B1 patent. More particularly, because of the small size and the requirement that only short (1-2 cm) lengths need to be used for blood glucose monitoring, it would require the half million stacking. This stacking can be simplified however, as contemplated by the practice of the present invention, by using large single fibers where no individual surface treatment need be applied. Thus, the cost of the complex process of the '737 patent to place surface texture on the associated fibers is unnecessarily and disadvantageously high.